A case of exacerbated encephalopathy with stroke-like episodes and lactic acidosis triggered by metformin in a patient with MELAS.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a maternally inherited multisystemic disorder caused by mutations in mitochondrial DNA that result in cellular energy deficiency. MELAS affects the most metabolically active organs, including the brain, skeletal muscles, cochlea, retina, heart, kidneys, and pancreas. As a result, about 85% of carriers of m.3243A > G, the most common mutation in MELAS, develop diabetes by the age of 70. Although metformin is the most widely prescribed drug for diabetes, its usefulness in mitochondrial dysfunction remains controversial. Here, we present the case of a 32-year-old Korean patient diagnosed with MELAS who presented with exacerbated stroke-like episodes and lactic acidosis triggered by metformin.

Genotype-phenotype analysis of MT-ATP6-associated Leigh syndrome.

OBJECTIVES: Mitochondrial DNA (mtDNA)-associated Leigh syndrome (LS) is characterized by maternal inheritance, and the heteroplasmic mutant load of mtDNA pathogenic variants is known to affect clinical phenotypes. Among mtDNA pathogenic variants, variants of the MT-ATP6 gene account for most of reported cases. In this report, we aimed to describe the clinical and genetic findings of MT-ATP6-associated LS patients diagnosed at a single tertiary institution in Korea. METHODS: Thirteen patients with genetically confirmed MT-ATP6-associated LS were selected. We reviewed each patient's clinical findings, including general characteristics, biochemical parameters, brain MR images, muscle biopsy results, and heteroplasmic mutant load over a long-term follow-up period. RESULTS: MT-ATP6-associated LS was of predominantly early onset (age <2 years), although we identified 2 late-onset (>60 months) LS patients. The heteroplasmic mutant load estimated by next-generation sequencing was 96%-100% in all nucleotide change groups. Compared with other forms of MT-ATP6-associated LS, the m.8993T>G point mutation elicited a significantly higher rate of symptom onset before 2 years of age. Brain MRI showed bilateral basal ganglia involvement in all patients, followed by cerebral atrophy, brainstem and thalamus involvement, and cerebellar atrophy. After follow-up (median 7.2 years, range 1.4 to 11.5 years), LS with m.8993T>G point mutations had a slightly more severe clinical progression compared with other forms of MT-ATP6-associated LS. CONCLUSIONS: MT-ATP6-associated LS patients presented with a broad spectrum of clinical diagnoses and had a very high heteroplasmic mutant load. This study provides valuable data on MT-ATP6-associated LS that will inform subsequent studies on LS.

Central precocious puberty may be a manifestation of endocrine dysfunction in pediatric patients with mitochondrial disease.

We retrospectively reviewed the data of 140 female pediatric patients with rare mitochondrial diseases (MDs) confirmed using muscle biopsy. We evaluated patients who were diagnosed with central precocious puberty (PP) with early pubertal development to determine whether PP is a clinical manifestation of MDs. We also examined the clinical, auxiological, laboratory, and radiological parameters after 1 year of gonadotropin-releasing hormone treatment for central PP. Among the 140 girls with MDs, 29 had early pubertal development and underwent endocrine evaluation. Ten (7.1%) patients were diagnosed with central PP; the prevalence of central PP was higher than was that previously thought. Patients with central PP exhibited bone age advancement over 1 year and increased sex hormone levels despite their young age at diagnosis. Serum estradiol levels were significantly higher in younger patients than in older patients (P = 0.004). Patients with central PP treated with gonadotropin-releasing hormone had favorable outcomes, and their pubertal development was suppressed for 1 year.Conclusion: Central PP may be a manifestation of endocrine dysfunction in young girls with MDs. What is Known: • The general characteristics of mitochondrial diseases include developmental delays and retarded growth. • Precocious puberty has rarely been suggested as a clinical manifestation of mitochondrial diseases. What is New: • Among the 140 girls with mitochondrial diseases, 10 (7.1%) were diagnosed with central precocious puberty. • Serum estradiol levels were significantly higher in younger patients than in older patients.

Focal cerebellar infarction as an initial sign of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a type of mitochondrial disorder and stroke-like lesions are observed prominently in the brain magnetic resonance imaging. Those stroke-like lesions of MELAS patients are usually located in the posterior quadrants and do not correspond to typical vascular territories. This case illustrates that focal cerebellar infarction can be the sole initial sign of MELAS.

Epilepsy-related clinical factors and psychosocial functions in pediatric epilepsy.

PURPOSE: The aim of this study was to identify the different influencing patterns of demographic and epilepsy-related variables on various aspects of psychosocial function in pediatric epilepsy. METHOD: Five hundred ninety-eight patients with pediatric epilepsy between the ages of 4 and 18 years (boys=360, 60% and girls=238, 40%) and their parents participated in the study. Parents completed the Social Maturity Scale (SMS), the Korean version of the Child Behavior Checklist (K-CBCL), and the Korean version of the Quality of Life in Childhood Epilepsy Questionnaire (K-QOLCE) to assess daily living function, behavior, and quality of life. The Children's Global Assessment Scale (CGAS) was completed by clinicians to assess general adaptive function. Demographic variables, such as age and sex of child, and epilepsy-related clinical variables, including seizure type, seizure frequency, duration of epilepsy, and number of medications, were obtained from medical records. RESULTS: Demographic and epilepsy-related clinical variables had a strong influence (22-32%) on the cognition-related domain such as general adaptive function, school/total competence, and quality of life for cognitive function while a comparatively smaller effect (2-16%) on the more psychological domain including behavioral, emotional, and social variables. Younger age, shorter duration of illness, and smaller number of medications showed a strong positive impact on psychosocial function in pediatric epilepsy, particularly for adaptive function, competence, and quality-of-life aspects. CONCLUSION: Given the wide range of impact of demographic and clinical variables on various facets of psychosocial functions, more specific understanding of the various aspects of factors and their particular pattern of influence may enable more effective therapeutic approaches that address both the medical and psychological needs in pediatric epilepsy.

Therapeutic outcome of patients with Lennox-Gastaut syndrome with mitochondrial respiratory chain complex I deficiency.

Background: Lennox-Gastaut syndrome (LGS), a severe developmental epileptic encephalopathy, has various underlying causes. Mitochondrial respiratory chain complex I (MRC I) deficiency is an important cause of metabolic disorders such as mitochondrial dysfunction that can compromise brain function, thereby causing intractable epilepsy, including LGS. Thus, it can be expected that the presence or absence of MRC I deficiency may affect the treatment outcome of patients with LGS. Objectives: In this retrospective study, we aimed to investigate differences in the epilepsy characteristics and treatment outcomes between patients with LGS with and without MRC I deficiency. Methods: We retrospectively reviewed the medical records of 92 patients with LGS. We divided 68 patients with LGS according to the presence (n = 30) or absence (n = 38) of MRC I deficiency and compared their epilepsy characteristics. Results: Generalized tonic and drop seizures were significantly worse in patients with LGS and MRC I deficiency than in those without MRC I deficiency group at the 1-year follow-up (p < 0.001) and final follow-up 1 (p < 0.001). Patients with LGS and MRC I deficiency had significantly fewer electroencephalogram (EEG) improvements compared to those without MRC I deficiency at the 1-year follow-up (p = 0.031). Additionally, in the final follow-up period, patients with LGS and MRC I deficiency had significantly less improvement in EEG findings compared to patients without MRC I deficiency (p < 0.001). Conclusion: The overall treatment prognosis-in terms of improvement in traumatic generalized tonic seizure, drop seizure, and EEG findings-is worse in patients with LGS and MRC I deficiency than that in patients with LGS but without MRC I deficiency. Additional and targeted treatment is required to treat LGS with MRC I deficiency.

Effects of the coronavirus disease outbreak on the development of neurological disorders in children: A comparison of the incidence of febrile seizure and epilepsy using an interrupted time-series approach.

BACKGROUND: With the outbreak of COVID-19, school closures and quarantines following social distancing have brought significant changes to children's lifestyles. Therefore, we aimed to compare the population-adjusted incidence of febrile seizures(FS) and epilepsy before and after the COVID-19 outbreak in Korea and to assess the effects of the COVID-19 outbreak on the incidence by region and age group. METHODS: A retrospective cohort study was conducted using nationwide claims data and covid data from January 2019 to December 2020. The incidence of diseases and difference in incidence before (Jan 20 to Dec 30, 2019) and after (Jan 20 to Dec 30, 2020) the COVID-19 outbreak was measured using rate ratio. An Interrupted time series analysis was used to identify the effect of COVID-19 on trends of FS and epilepsy. Subgroup analysis by age, sex, insurance, and risk of coronavirus by area were conducted. RESULTS: Following the onset of the pandemic, the number of newly diagnosed FS cases decreased sharply by 69 % (24,182 to 7238), whereas the incidence of epilepsy, increased to 1.02 times (30,286-29,312), when adjusted in proportion to the population. Notably, a greater decrease in the incidence of FS were found in the regions with high-risk of coronavirus. A result of segmented regression analysis proved the decrease was significant and made immediately after the pandemic started(p < 0.001). In contrast to the incidence of FS, that of epilepsy did not exhibit a significant month-to-month change during the baseline period, immediately after the pandemic started, and during the pandemic. CONCLUSIONS: The COVID-19 outbreak and resulting social distancing measures reduced the incidence of febrile seizure immediately rather than gradually. Unlike in the case of acute febrile seizure, the COVID-19 pandemic had no effect on the incidence of chronic epilepsy.

Heteroplasmic Mutant Load Differences in Mitochondrial DNA-Associated Leigh Syndrome.

BACKGROUND: Mitochondrial DNA (mtDNA)-associated Leigh syndrome is influenced by mutant pathogenicity and corresponding heteroplasmic loads; however, the manner in which heteroplasmic mutant load affects patient phenotypes and the relationship between mutant types and heteroplasmic mutant loads remain unknown. We aimed to investigate the distribution of the mutant load of different mtDNA mutations in a single-center cohort. METHODS: We used next-generation sequencing to confirm mtDNA mutations in 31 patients with Leigh syndrome. Subsequently, we counted the number of mtDNA reads to quantitatively analyze the heteroplasmic mutant load and categorize the patients according to the mtDNA mutations they harbored. Confirmed cases of mtDNA-associated Leigh syndrome were classified according to the mutations observed in six genes and 10 nucleotides. RESULTS: Of the 31 patients with Leigh syndrome, 27 harbored known pathogenic mutations. We discovered that MT-ATP6 was the most commonly mutated gene (n = 13 patients), followed by MT-ND3 (n = 7) and MT-ND5 (n = 4). MT-ATP6 had a significantly higher mutant load than MT-ND3 and MT-ND5 (P < 0.001, each). By contrast, MT-ND5 had a significantly lower mutant load than MT-ND3 (P = 0.007). Notably, the mutation loads varied significantly among patients carrying the MT-ATP6, MT-ND3, and MT-ND5 mutations. CONCLUSIONS: Our study illustrated the heteroplasmic diversity and phenotypic expression threshold of mutated mitochondrial genes in mtDNA-associated Leigh syndrome. The results provide promising insights into the genotype-phenotype correlation in mtDNA-associated Leigh syndrome that are expected to guide the development of tailored treatments for Leigh syndrome.

Nutritional Intervention Through Ketogenic Diet in GLUT1 Deficiency Syndrome.

Glucose transporter type 1 (GLUT1) deficiency syndrome (DS) is a metabolic brain disorder caused by a deficiency resulting from SLC2A1 gene mutation and is characterized by abnormal brain metabolism and associated metabolic encephalopathy. Reduced glucose supply to the brain leads to brain damage, resulting in delayed neurodevelopment in infancy and symptoms such as eye abnormalities, microcephaly, ataxia, and rigidity. Treatment options for GLUT1 DS include ketogenic diet (KD), pharmacotherapy, and rehabilitation therapy. Of these, KD is an essential and the most important treatment method as it promotes brain neurodevelopment by generating ketone bodies to produce energy. This case is a focused study on intensive KD nutritional intervention for an infant diagnosed with GLUT1 DS at Gangnam Severance Hospital from May 2022 to January 2023. During the initial hospitalization, nutritional intervention was performed to address poor intake via the use of concentrated formula and an attempt was made to introduce complementary feeding. After the second hospitalization and diagnosis of GLUT1 DS, positive effects on the infant's growth and development, nutritional status, and seizure control were achieved with minimal side effects by implementing KD nutritional intervention and adjusting the type and dosage of anticonvulsant medications. In conclusion, for patients with GLUT1 DS, it is important to implement a KD with an appropriate ratio of ketogenic to nonketogenic components to supply adequate energy. Furthermore, individualized and intensive nutritional management is necessary to improve growth, development, and nutritional status.

Nusinersen for spinal muscular atrophy types II and III: a retrospective single-center study in South Korea.

BACKGROUND: This study investigated the efficacy and safety of nusinersen, an antisense oligonucleotide, in patients with spinal muscular atrophy (SMA) types II (OMIM: 253,550) or III (OMIM: 253,400), including those with severe scoliosis or requiring respiratory support via mechanical ventilation. METHODS: Data from 40 patients with genetically confirmed SMA who were treated with nusinersen at our institute from March 2019 to April 2022 were retrospectively analyzed. Of these, 30 patients with an age of onset < 3 years and not on permanent ventilation were selected. Clinical and genetic characteristics were investigated, and motor function was evaluated based on the Hammersmith Functional Motor Scale-Expanded (HFMSE) score. RESULTS: The mean age of symptom onset was 1.2 years. Most patients were diagnosed with SMA type II (27/30, 90%). Nusinersen was administered via computed tomography-guided or direct intrathecal injection in 87% (26/30) and 13% (4/30) of the patients, respectively. At the 6-, 14-, 22-, and 26-month follow-ups, 72%, 71%, 88%, and 86% of patients showed motor improvement, respectively, with mean changes in HFMSE scores of 2.10, 2.88, 4.21, and 5.29, respectively. Multivariable analysis showed that the use of noninvasive ventilation was associated with poorer outcomes of motor function. CONCLUSIONS: Patients with SMA type II or III who received nusinersen treatment showed significant improvement in motor function. A longer treatment duration led to a higher number of patients with improved motor function. No significant side effects of nusinersen were observed. Patients with SMA, even those with severe scoliosis or on respiratory support, can be safely treated using nusinersen.

Nusinersen for Spinal Muscular Atrophy Type I with Chronic Respiratory Failure: A Retrospective Study in South Korea.

PURPOSE: To analyze the efficacy and safety of nusinersen in patients with spinal muscular atrophy (SMA) type I with chronic respiratory failure. MATERIALS AND METHODS: We retrospectively reviewed seven patients diagnosed with SMA type I and chronic respiratory failure who were on permanent ventilation and treated with nusinersen at Gangnam Severance Hospital between January 2018 and July 2023. Patient demographics and clinical characteristics were recorded, and treatment progress was evaluated according to Hammersmith Infant Neurological Examination (HINE-2) and Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) scores. RESULTS: Patients initially developed hypotonia at a mean age of 3.7 months. Mean age at start of nusinersen was 7.3 years; the mean duration of follow-up after starting nusinersen was 46.2 months. At 6-, 18-, 38-, 58-, and 74-month follow-up, the mean changes in CHOP-INTEND scores were 1.0, 2.9, 1.8, 1.5, and 1.5, respectively, and the proportions of patients who showed disease amelioration were 28.6%, 71.4%, 75.0%, 100%, and 100%, respectively. CONCLUSION: Nusinersen is safe and effective in patients with SMA type I, even those with chronic respiratory failure and those on permanent ventilation. No significant adverse effects of nusinersen were observed.

Nusinersen demonstrates effectiveness in treating spinal muscular atrophy: findings from a three-year nationwide study in Korea.

Introduction: Nusinersen is the first drug approved for spinal muscular atrophy (SMA) treatment. In this study, we aimed to evaluate the long-term safety and efficacy of nusinersen, assess the therapeutic effects based on the treatment initiation timing and baseline motor function, and explore the perception of functional improvement from either parents or patients, utilizing 3-year nationwide follow-up data in South Korea. Methods: We enrolled patients with SMA who were treated with nusinersen under the National Health Insurance coverage, with complete motor score records available and a minimum treatment duration of 6 months. To evaluate the motor function of patients, the Hammersmith Infant Neurological Examination-2 (HINE-2) was used for type 1 and the Expanded Hammersmith Functional Motor Scale (HFMSE) was used for types 2 and 3 patients. A significant improvement was defined as a HINE-2 score gain ≥5 for patients with type 1 and an HFMSE score ≥ 3 for patients with types 2 and 3 SMA. Effects of treatment timing were assessed. Patients with type 2 were further categorized based on baseline motor scores for outcome analysis. We also analyzed a second dataset from five tertiary hospitals with the information on parents/patients-reported impressions of improvement. Results: The study comprised 137 patients, with 21, 103, and 13 patients representing type 1, 2, and 3 SMA, respectively. At the 3-year follow-up, the analysis encompassed 7 patients with type 1, 12 patients with type 2, and none with type 3. Nearly half of all enrolled patients across SMA types (42.8, 59.2 and 46.2%, respectively) reached the 2-year follow-up for analysis. Patients with type 1 SMA exhibited gradual motor function improvement over 1-, 2-, and 3-year follow-ups (16, 9, and 7 patients, respectively). Patients with type 2 SMA demonstrated improvement over 1-, 2-, and 3-year follow-ups (96, 61 and 12 patients, respectively). Early treatment from symptom onset resulted in better outcomes for patients with type 1 and 2 SMA. In the second dataset, 90.7% of 108 patients reported subjective improvement at the 1-year follow-up. Conclusion: Nusinersen treatment for types 1-3 SMA is safe and effective in long-term follow-up. Early treatment initiation was a significant factor affecting long-term motor outcome.

Efficacy of VeinViewer in pediatric peripheral intravenous access: a randomized controlled trial.

UNLABELLED: Peripheral venous access in infants and children is technically challenging, because their veins are small and located deep in subcutaneous tissue, which makes them difficult to palpate or visualize. The VeinViewer® (Luminetx Corporation, Memphis, TN, USA) is a near-infrared light device that delineates the running course of subcutaneous veins. In this study, we investigated whether the use of the VeinViewer® in infants and children facilitated peripheral venous access, especially in difficult cases. This study was a randomized, controlled trial of a convenience sample of pediatric patients between the ages of 1 month and 16 years who required peripheral venous access in the pediatric ward. Prior to randomization, difficult intravenous access (DIVA) score, a four-variable clinical prediction rule for first-attempt success, was estimated. We compared the first-attempt success rates and procedural times between the VeinViewer® group and a control group. We evaluated 111 patients: 54 in the VeinViewer® group and 57 in the control group. Patient demographics and factors related to the success of vein access were similar for both groups. The overall first-attempt success rate was 69.4%: i.e., 77/111 in the VeinViewer® group and 38/57 in the control group, a difference that was not statistically significant. However, the first-attempt success rate increased from 5/20 in the control group to 14/24 in the VeinViewer® group for difficult veins with a DIVA score greater than 4 (p=0.026). There were no significant differences in procedural time between the two groups. CONCLUSION: The VeinViewer® facilitated peripheral venous access for pediatric patients with difficult veins, which enhanced first-attempt success rates.

Early cardiac evaluation in children with non-specific mitochondrial disease with isolated mitochondrial respiratory chain complex I defect.

AIMS: We evaluated echocardiography and electrocardiography (ECG) results in children with non-specific mitochondrial disease (MD) in order to study early cardiac involvement, a well-known complication of the disease. METHODS: Among non-specific MD children whose isolated mitochondrial respiratory chain complex I defect was confirmed by muscle biopsy and satisfied the criteria of MD, 27 who had no cardiac symptoms were evaluated by echocardiography and ECG. RESULTS: Three (11.1%) out of the 27 non-specific MD patients had left ventricular ejection fraction of less than 55% and two of them (7.4%) had fractional shortening of less than 26%. ECG abnormalities were observed in 16 of the non-specific MD patients (59.3%). Prolongation of heart rate-corrected QT interval was seen in 11 (40.7%) and widening of the QRS interval in eight (29.6%). Left ventricular ejection fraction and fractional shortening of the patients were significantly decreased compared with those in the control group while heart rate-corrected QT interval was prolonged in the former group. QRS interval was more widened in non-specific MD patients, but without statistical significance. CONCLUSION: The potentially severe cardiac involvement observed in our subjects suggests that early cardiac evaluation after confirming the diagnosis of MD and regular follow-up tests should be strongly recommended in children even in cases without typical cardiac manifestations.

Effective application of corpus callosotomy in pediatric intractable epilepsy patients with mitochondrial dysfunction.

Background: Whether epilepsy surgery, such as corpus callosotomy is effective in patients with pediatric intractable epilepsy with mitochondrial dysfunction is controversial, and there is a paucity of literature on this issue. Objective: This study aimed to assess and describe the effective application of corpus callosotomy for treating pediatric patients with intractable epilepsy with mitochondrial dysfunction in a single institution in Korea. Methods: This was a retrospective study of pediatric patients with intractable epilepsy and mitochondrial dysfunction who underwent corpus callosotomy in a single tertiary care center. Ten patients with intractable epilepsy with mitochondrial dysfunction were included, and 10 patients with intractable epilepsy with non-mitochondrial dysfunctions were included as a control group. The outcomes of corpus callosotomy in the two groups were evaluated and compared. Results: Corpus callosotomy was safely performed and was efficacious in reducing seizure frequency in both groups. The group with non-mitochondrial dysfunction showed slightly better treatment outcomes, with greater reductions in overall seizures, traumatic falling seizures, and electroencephalography improvements, but the differences in treatment effects were not statistically significant. Conclusions: Our study is meaningful as it identified the use of corpus callosotomy as a means to save lives and improve quality of life by reducing the frequency of seizures and those associated with traumatic falling in pediatric patients with intractable epilepsy with mitochondrial dysfunction. Larger multicenter studies are necessary to confirm the efficacy of the procedure.

Complete Penetrance but Different Phenotypes in a Korean Family with Maternal Interstitial Duplication at 15q11.2-q13.1: A Case Report.

The 15q duplication syndrome (dup15q) is due to the presence of at least one additional derived copy of the Prader-Willi syndrome/Angelman syndrome (PWS/AS) critical region that is approximately 5 Mb long within chromosome 15q11.2-q13.1. This report describes distinct roles of the origin of interstitial (int) dup15q underlining the critical importance of maternally active imprinted genes in the contribution to complete penetrance but different phenotypes of neuropsychotic disorders such as schizophrenia (SCZ) and autism spectrum disorder (ASD) in a Korean family. The proband's mother as a consultant visited our hospital for her offspring's genetic counseling and segregation analysis. She had two daughters diagnosed as SCZ or ASD and one son diagnosed as ASD. To resolve the potential genetic cause of SCZ and ASD in the proband and her sibling, whole genomic screening of chromosomal rearrangements by array-comparative genomic hybridization (CGH) was performed using SurePrint G3 Human CGH + SNP Microarray 4 × 180 K. Results of the array-CGH analysis revealed an interstitial duplication at 15q11.2-q13.1 (duplication size of 5.4 Mb) in the mother and her three offspring with SCZ or ASD. Our case, together with previous findings of high occurrence of psychotic disorder, suggest that maternally expressed gene product in the critical region of PWS/AS might mediate the risk of neurodevelopmental disorder (ASD) as well as psychotic disorder (SCZ). Multiple cytogenetic and molecular methods are recommended for investigating children with 15q11.2-q13.1 duplication and neuropsychotic disorders.

Epidemiological Features and Economic Burden of Guillain-Barré Syndrome in South Korea: A Nationwide Population-Based Study.

BACKGROUND AND PURPOSE: Guillain-Barré syndrome (GBS) is rare, but its symptoms are severe and they occasionally lead to long-term disability. Country-specific epidemiological evidence is useful for detecting potential problems at the population level. This study investigated the epidemiological and economic characteristics of GBS in South Korea. METHODS: The Korean National Health Insurance Service claims data from 2010 to 2016 were used to identify incident cases as newly hospitalized patients with a primary diagnosis of GBS (the 10th revision of the International Classification Disease code of G61.0). New cases were defined as patients not having claim records for GBS within one year prior to the hospital admission for GBS. RESULTS: The incidence rate increased by 45.6% between 2010 and 2016, from 1.28 to 1.82 per 100,000 population. All age groups other than <20 years showed increasing trends. The incidence rate was highest in those aged 65 years to 74 years. Approximately 72% of the incident GBS cases had antecedent infection within 42 days before GBS was diagnosed. Children younger than 10 years constituted the highest proportion of antecedent infections (93.7%). The average length of stay per GBS hospitalization was 33.5 days. Patients had an average of 7.48 outpatient visits for GBS treatment per year. The economic burden from a societal perspective of treating GBS during the first year was USD 16,428. CONCLUSIONS: The increasing incidence trend and substantial economic burden of GBS strongly advocate the development of effective strategies for preventing and managing GBS.